Thursday, February 16, 2012

Mitosis mystery: Solved

Ever wonder HOW those chromosomes all lined up during mitosis?

It was something that was just glossed over when I took biology ... so long ago. It had to do something with microtubules... or something. Well, the mystery was recently solved. First, a more technical statement of what was known:

Thread-like proteins, called microtubules, extend from one of two spindle poles on either side of the cell and attempt to latch onto the duplicated chromosomes. This entire "spindle" structure acts to physically distribute the chromosomes, but it is not free floating in the cell. In addition to microtubules from both spindle poles that attach to all of the chromosomes, astral microtubules that are connected to the cell cortex—a protein layer lining the cell membrane—act to pull the spindle poles back and forth within the cell until the spindle and chromosomes align down the center axis of the cell. Then the microtubules tear the duplicated chromosomes in half, so that ultimately one copy of each chromosome ends up in each of the new daughter cells.

And then here's the bit that's new:

As Kiyomitsu watched mitosis unfold in symmetrically dividing human cells, he noticed that when the spindle oscillates toward the cell's center, a partial halo of the protein dynein lines the cell cortex on the side farther away from the spindle. As the spindle swings to the left, dynein appears on the right, but when the spindle swing to the right, dynein vanishes and reappears on the left side.

For Kiyomitsu, the key to the alignment mystery was dynein, which is known as a motor protein that "walks" molecular cargoes along microtubules. Kiyomitsu determined that in this case, dynein is anchored to the cell cortex by a complex that includes the protein LGN, short for leucine-glycine-asparagine-enriched protein. Instead of moving along an astral microtubule, the stationary dynein acts as a winch to pull on the spindle pole, and the microtubules and chromosomes attached to it, toward the cell cortex.

So there you go: dynein causes your chomosomes to make a nice straight line out of a mess of the chromosomes. But to make it a little technical:

After testing a couple of signaling molecules associated with chromosomes, Kiyomitsu determined that a signal from the chromosomes, involving the ras-related nuclear protein (Ran), blocks LGN, and therefore dynein, from attaching to the cell cortex closest to the chromosomes. Ran bound to guanosine-5'-triphosphate (Ran-GTP), which controls nuclear import in the interphase stage of mitosis, had previously been suggested to control spindle assembly during mitosis in germ cells, but roles for the Ran gradient in mitotic non-germ cells were unclear. Kiyomitsu's work suggests a key role for Ran in directing spindle orientation.